Dichloromethane → (R)-N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-methylbenzamide hydrochloride

HRID 875682Notes

Reaction equation

HRID 875682 reaction equation
[Br:1][C:2]1[C:3]([N:21]2[CH2:26][CH2:25][CH2:24][C@@H:23]([NH:27]C(=O)OC(C)(C)C)[CH2:22]2)=[C:4]2[C:10]([NH:11][C:12](=[O:20])[C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[CH:14]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.C(O)(C(F)(F)F)=O.C(Cl)[Cl:43]>>[ClH:43].[NH2:27][C@@H:23]1[CH2:24][CH2:25][CH2:26][N:21]([C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]3[NH:8][CH:9]=[C:10]([NH:11][C:12](=[O:20])[C:13]4[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[CH:14]=4)[C:4]=23)[CH2:22]1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 67045390(R)-tert-butyl 1-(5-bromo-3-(3-methylbenzamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 67045388(R)-N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-methylbenzamide hydrochlorideYield 87.4%

Procedure

(R)-tert-Butyl 1-(5-bromo-3-(3-methylbenzamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (123 mg, 0.233 mmol) in DCM (3 mL) at room temperature was treated with TFA (1 mL), and the reaction was stirred for 1 hour. The reaction mixture was then concentrated to dryness. The resulting residue was dissolved in minimal DCM and added to a stirring solution of 1M HCl in ether. The solid formed was filtered, washed with ether and dried to give (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-methylbenzamide hydrochloride (0.102 g, 87.4% yield). 1H NMR (400 MHz, D2O) δ 8.02 (s, 1H), 7.64 (s, 1H), 7.62-7.52 (m, 1H), 7.42-7.38 (m, 3H), 3.49-3.42 (m, 1H), 3.27-3.18 (m, 2H), 3.17-3.06 (m, 2H), 2.29 (s, 3H), 1.81-1.71 (m, 1H), 1.68-1.57 (m, 1H), 1.49-1.26 (m, 2H); LCMS (APCI+) m/z 428, 430 (M+H)+, Retention time=2.68 minutes (Method 2).

Workup

  1. concentrationThe reaction mixture was then concentrated to dryness
  2. dissolutionThe resulting residue was dissolved in minimal DCM
  3. additionadded to a stirring solution of 1M HCl in ether
  4. customThe solid formed
  5. filtrationwas filtered
  6. washwashed with ether
  7. customdried

Sources & evidence

ORD record
ord-9cb80cc8bcf84e6ca7de948046ca36d5
Source dataset
uspto-grants-2015_03
Patent number
US08981085B2

Reaction notes

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